Objective To investigate the differences in external nasal morphological measurements among children aged 12-16 years in the Qingdao region for sex and age estimation. Methods Multi-slice spiral computed tomography images of 159 Han children aged 12-16 years from the Qingdao region were selected. External nasal morphological measurements were mea-sured, including 11 linear distances, 2 angles, and 7 proportional indices, based on which the nasal type of each child was determined. Children were grouped by sex and age, and the aforementioned measurements were compared across groups. Receiver ope-rating characteristic (ROC) curves were used to evaluate the discriminative efficacy of measurements showing significant differences for sex and age estimation. Results In this study, the nasal type of Han children aged 12-16 years in the Qingdao region was predominantly leptorrhine, followed by mesorrhine, while hyperleptorrhine and platyrrhine nasal types were less common. There were statistically significant differences between boys and girls in 10 linear distances (nasal depth, nasal width, nasal tip width, nasal height, nasal length, intercanthal distance, alar length, alar thickness, columella width, and nasal root width), 4 proportional indices (nasal index, nasal depth-nasal width index, nasal width-intercanthal distance index, and alar length-nasal height index), and the nasofrontal angle (Z=-7.27--4.77,t=1.99-7.69,P<0.05). There were significant differences in nasal length, nasal width, intercanthal distance, alar length, columella width, nasal tip width, nasofrontal angle, nasal tip angle, nasal index, nasal width-intercanthal distance index, and alar length-nasal height index among different age groups of boys (H=6.18-25.69,P<0.05). There were significant differences in nasal depth and nasal tip angle across age groups of girls (H=6.33, 6.06,P<0.05). ROC curves showed that the nasofrontal angle and nasal depth-nasal width index exhibited good discriminative efficacy for sex determination in Han children aged 12-16 years in the Qingdao region (area under the ROC curve=0.71,0.63), while the nasal tip angle and nasal index showed good discriminative efficacy for age determination (area under the ROC curve=0.65-0.72). Conclusion The nasofrontal angle and nasal depth-nasal width index show good discriminative efficacy for determining the sex of Han children aged 12-16 years in the Qingdao region, and the nasal tip angle and nasal index show good discriminative efficacy for determining their age. The aforementioned measurements are recommended for sex and age estimation in forensic individual identification for this population.
Objective To investigate the role and potential mechanism of PIWI-interacting RNAs (piRNAs) in the pa-thogenesis of alcoholic cardiomyopathy (ACM). Methods A mouse model of ACM was established (ACM group), and a corresponding normal control group was established. High-throughput RNA sequencing was used to identify differentially expressed piRNAs in cardiac tissue between the two groups, and their target gene networks were constructed. RT-qPCR was used to measure the expression levels of the differentially expressed piRNAs, and the GO/KEGG enrichment analyses were used to explore their functional roles and related pathways. In vitro, rat H9c2 cardiomyocytes were transfected with piRNA mimic negative control fragment (group A), piR-0130 mimic (group B), piRNA inhibitor negative control fragment (group C), and piRNA inhibitor (group D), respectively. In parallel, alcohol stimulation was performed in addition to the above procedures (groups a-d). RT-qPCR was used to measure the relative mRNA expression levels of the inflammatory cytokines TNF-α, IL-6, and IL-10 in H9c2 cells, and Wes-tern blotting was used to measure the relative expression levels of the apoptosis-related proteins p53 and Cleaved Caspase-3. Results High-throughput RNA sequencing identified 2 276 differentially expressed piRNAs in cardiac tissue between the ACM group and the control group, among which there were 1 875 upregulated piRNAs and 401 downregulated piRNAs, and further analysis showed that piR-0130, piR-0220, and piR-0255 were the three piRNAs with the most significant differential expression. RT-qPCR showed that piR-0130, piR-0220, and piR-0255 were significantly upregulated in cardiac tissue of ACM mice (t=9.62-22.99,P<0.01). The GO/KEGG enrichment analyses showed that the differentially expressed piRNAs were mainly involved in the regulation of cardiomyocyte metabolism, cardiomyocyte apoptosis, and inflammatory responses. RT-qPCR and Western blotting showed that before and after alcohol stimulation, piR-0130 overexpression significantly upregulated the mRNA expression levels of TNF-α and IL-6 and the protein expression levels of p53 and Cleaved Caspase-3 in rat H9c2 cells (F=45.55-156.86,tDunnett=3.57-10.17,t=7.30,8.38,P<0.05) and significantly downre-gulated the mRNA expression level of IL-10 (tDunnett=5.34,7.73,P<0.05); on the contrary, inhibition of piR-0130 significantly reduced the mRNA expression levels of TNF-α and IL-6 and the protein expression levels of p53 and Cleaved Caspase-3 (F=99.60-221.90,tDunnett=4.05-10.68,t=3.04,6.21,P<0.05) and significantly increased the mRNA expression level of IL-10 (tDunnett=2.07,11.15,P<0.05). Conclusion This study shows significantly abnormal expression of piR-0130, piR-0220, and piR-0255 in cardiac tissue of ACM mice, among which piR-0130 may be involved in the development and progression of ACM by regulating inflammatory response and the apoptosis pathway mediated by p53/Cleaved Caspase-3.
Objective To investigate the effect of different root canal preparation techniques on the biomechanics of cracked maxillary second premolars. Methods A three-dimensional finite element model was established for a maxillary second premolar and its periodontal tissue based on the cone-beam computed tomography data from one adult volunteer. Three cracked tooth models were constructed according to crack depth, i.e., enamel crack (Crack A), superficial dentin crack (Crack B), and middle dentin crack (Crack C). Nine maxillary second premolars with Vertucci type Ⅰ root canal morphology were randomly divi-ded into group K (root canal preparation using stainless steel K-files with step-back technique), group P (ProTaper nickel-titanium rotary files with crown-down technique), and group T (TF-Adaptive system), followed by obturation and coronal restoration. The three preparation methods were combined with the three crack types in pairs to construct nine experimental models. The finite element analysis was used to investigate the Von Mises stress distribution characteristics of each model under a vertical load of 200 N along the long axis and an oblique load of 200 N at 45° to the long axis. Results Stress concentration was located at the loading point and crack margins in all groups under both loading conditions. Under the vertical loading, the extent of stress concentration at crack margins in Crack B and Crack C was greater than that in Crack A, with Crack C being the most significant. Under the oblique loading, a high-stress zone was only detected at the resin-tooth interface in Crack C. Under the same crack conditions, group P had the highest peak Von Mises stress, followed by group K and group T, with similar results between group T and group N (unprepared control group), and the differences between groups increased with the increase in crack depth. Conclusion For cracked maxillary second premolars, root canal preparation using the TF-Adaptive system with its small taper and adaptive motion mode has a relative minimal impact on tooth stress distribution and could better maintain a biomechanical state close to that of a natural tooth.
Objective To investigate the association of telomerase reverse transcriptase (TERT) gene promoter mutations with the clinicopathological features and prognosis of patients with phyllodes tumor (PT) of the breast. Methods PT surgical specimens were collected from the archives of 306 patients in Department of Pathology in The Affiliated Hospital of Qingdao University and Linyi Central Hospital from 2014 to 2021. Sanger sequencing was used to detect the status of TERT promoter mutation, and then the patients were divided into mutant group and wild-type group. The two groups were compared in terms of age, clinicopathological features (tumor histological grade, maximum tumor diameter, tumor stromal cell density, stromal nuclear atypia, mitotic count, and degree of stromal overgrowth), and postoperative recurrence, and the univariate and multivariate Cox proportional hazards models were used to evaluate the influence of each clinicopathological parameter on the postoperative recurrence of PT. Results Among the 306 patients with PT, 129 patients (42.2%) harbored TERT gene promoter mutations, among which c.-124C>T was the main mutation type (88.4%). There were significant differences between the two groups in tumor histological grade, maximum tumor diameter, stromal cell density, stromal nuclear atypia, mitotic count, and degree of stromal overgrowth (χ2=32.476-69.258, P<0.001), and compared with the wild-type group, the mutant group had a significantly higher proportion of patients with postoperative recurrence (χ2=9.652, P<0.001). The univariate Cox proportional hazards model analysis showed that TERT promoter mutation, maximum tumor diameter, stromal cell density, stromal nuclear atypia, mitotic count, and degree of stromal overgrowth were influencing factors for postoperative recurrence of PT, and the multivariate Cox proportional hazards model analysis showed that mitotic count ≥5 per 2 mm2 was an independent risk factor for postoperative recurrence (P<0.05), whereas TERT gene promoter mutation did not demonstrate independent predictive significance (P=0.581). Conclusion TERT gene promoter mutation is significantly associated with tumor histological grade, maximum tumor diameter, stromal cell density, stromal nuclear atypia, mitotic count, degree of stromal overgrowth, and recurrence, while it is not an independent risk factor for the recurrence of PT.
Objective To investigate the value of terahertz three-dimensional (3D) tomography in differentiating central tumor tissue from adjacent normal tissue in a nude mouse model of lung adenocarcinoma. Methods A nude mouse model of subcutaneous lung adenocarcinoma was successfully established, and then small-animal micro-CT and reflective terahertz 3D tomography were used for in vivo scanning. HE-stained sections were prepared for tumor tissue and lung tissue, and histopathological observation and transmission terahertz time-domain spectroscopy were used to analyze the optical characteristics of ex vivo tissue. Results Reflective terahertz 3D tomography showed that terahertz signal intensity in the tumor center tissue was significantly higher than that in adjacent normal tissue. The contrast ratio reached approximately 12∶1 in terahertz time-domain 3D tomography, and the highest contrast ratio of approximately 19∶1 was observed at 0.5 THz for terahertz frequency-domain 3D tomography. The spectral analysis of ex vivo tissue showed that the refractive index of tumor center within the range of 0.1-1.6 THz was significantly higher than that of normal lung tissue, with the absorption coefficient showing distinct peaks at 1.5 THz and 1.9 THz. There were significant differences in both the real and imaginary parts of the permittivity between tumor tissue and normal lung tissue (P<0.05). Histopathological examination further confirmed disordered arrangement of tumor cells in tumor tissue, with nuclear hyperchromasia and increased microvascular density, which were consistent with terahertz spectral signatures. Conclusion Terahertz technology can effectively detect the differences in optical parameters between tumor tissue and adjacent normal tissue in lung adenocarcinoma, achieve high-contrast in vivo imaging and ex vivo identification, and provide a new direction for the early detection of lung adenocarcinoma, thereby showing promising application prospects in clinical practice.
Objective To investigate the age-related changes of MRI diffusion-weighted imaging (DWI) signal intensity of bone marrow in different regions of the skull in normal children. Methods A total of 1 356 normal children who underwent cranial MRI-DWI in Department of Radiology, The Affiliated Hospital of Qingdao University, were enrolled, and according to their age, they were divided into infant and toddler group, preschool group, school-aged group, and adolescence group. A semi-quantitative method was used to measure DWI signal intensities of bone marrow at seven skull regions (frontal bone, bilateral temporal bones, bilateral parietal bones, occipital bone, sphenoid bone, bilateral mandibular condyle, and clivus). Bone marrow signal intensities were compared between the four groups, and the Pearson correlation coefficient was used to investigate the correlation between age and DWI signal intensity of bone marrow at different regions of the skull. Results In the infant and toddler group, grade 3 DWI signals were mainly observed for bone marrow at different regions of the skull; in the preschool group, grade 1 low signals were mainly observed in the frontal and parietal bones, grade 2 transitional signals were mainly observed in the temporal, sphenoid, and occipital bones, and grade 3 high signals were mainly observed in the mandibular condyle and clivus; in the school-aged group, grade 1 low signals were mainly observed in the frontal, parietal, temporal, and sphenoid bones, while grade 2 transitional signals were mainly observed in the occipital bone, mandibular condyle, and clivus; in the adolescence group, the signals in the frontal, parietal, temporal, and sphenoid bones were basically converted to grade 1 signals, and the signals in the occipital bone, mandibular condyle, and clivus were reduced and were gradually converted to grade 1 low signals. The univariate analysis showed that there were significant differences between the four groups in DWI signal intensities of bone marrow at different regions of the skull (H=374.378-809.136,P<0.001); the DWI signal intensities of bone marrow in the frontal, temporal, parietal, and occipital bones decreased with age before the school-aged period (P<0.05); the DWI signal intensity of bone marrow in the mandibular condyle began to decrease with age since the preschool period (P<0.05); the DWI signal intensities of bone marrow in the sphenoid bone and clivus decreased over age across all age groups (P<0.05). The Pearson correlation analysis showed that the MRI-DWI signal intensities of bone marrow in all measured regions of the skull were significantly negatively correlated with age (r=-0.746--0.565,P<0.05). Conclusion DWI signals of bone marrow in the skull of normal children tend to decrease regularly with the increase in age, with anatomical heterogeneity in the timing and rate of signal reduction across different skull regions, characterized by the earliest signal transition in the calvaria and the latest in the skull base. This study provides important imaging evidence for physiological and pathological research on skull bone marrow in children.
Objective To construct a Lactococcus lactis strain capable of expressing urate oxidase, and to investigate its efficacy and safety in reducing uric acid in a mouse model of hyperuricemia. Methods Lactococcus lactis NZ3900 was used as a chassis to construct an engineered bacterial strain, and Western blotting was used to examine the expression of histidine tag in this strain. A microplate reader was used to measure the content of the parental strain and the engineered strain (expressed as OD va-lues) at 0, 4, 8, 12, 16, 20, and 24 hours of culture, as well as the activity of urate oxidase in the engineered strain. Specific pathogen-free male Kunming mice were randomly divided into control group (intragastric administration and intraperitoneal injection of sodium carboxymethyl cellulose solution), model group (intragastric administration of hypoxanthine and intraperitoneal injection of potassium oxonate), allopurinol group (intragastric administration of hypoxanthine+allopurinol and intraperitoneal injection of potassium oxonate), and engineered strain group (intragastric administration of hypoxanthine and the engineered strain and intraperitoneal injection of potassium oxonate). On day 29, the serum levels of uric acid, creatinine, blood urea nitrogen, and TNF-α were measured for the mice in each group, as well as the activity of xanthine oxidase in the liver and the content of fecal uric acid, and renal histopathological changes were observed for all groups. Results The expression of histidine tag was detected in the engineered strain. Over the time of culture, the OD values of both the parental strain and the engineered strain first increased and then decreased (F=941.27,937.76,P<0.05), and the engineered strain showed the highest OD value and the highest activity of urate oxidase at 20 hours (P<0.05). Compared with the control group, the model group had significant increases in serum uric acid and creatinine (q=20.19,6.15,P<0.05); compared with the model group, the allopurinol group had significant increases in serum creatinine and blood urea nitrogen (q=4.94,14.70,P<0.05); the engineered strain group had a significantly lower level of serum uric acid than the model group (q=5.47,P<0.05); the allopurinol group had a significantly lower hepatic XOD activity than the model group (q=31.39,P<0.05); the model group had a significant higher content of fecal uric acid than the control group, and the engineered strain group had a significant lower content of fecal uric acid than the model group (q=8.28, 6.64,P<0.05). HE staining showed that compared with the model group, the engineered strain group had a basically normal glomerular architecture and regular morphology of renal tubular epithelial cells. Conclusion This study successfully constructed a Lactococcus lactis strain capable of expressing urate oxidase, and this strain can significantly reduce serum uric acid, creatinine, blood urea nitrogen, and TNF-α in a mouse model of hyperuricemia and effectively alleviate renal injury, with a favorable safety profile.
Objective To investigate the effect of compound 1-13 on melanogenesis of melanoma cells and Parkinson’s disease (PD)-like injury. Methods Enzyme activity assay was used to observe the effect of compound 1-13 on tyrosinase activity. MTT assay was used to measure the viability of mouse melanoma B16F10 cells treated with compound 1-13 at concentrations of 0, 1, 5, 10, 20, 50, and 100 μmol/L. B16F10 cells were divided into groups a-h. The cells in group a were not given any treatment; the cells in group b were treated with 1 mmol/L 1-methyl-4-phenylpyridinium iodide (MPP+) solution; the cells in groups c, d, and e were pretreated with kojic acid at concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, for 1 hour, followed by the addition of 1 mmol/L MPP+ solution; the cells in groups f, g, and h were pretreated with compound 1-13 at concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, for 1 hour, followed by the addition of 1 mmol/L MPP+ solution. MTT assay was used to measure the viability of cells in groups a-h. B16F10 cells were divided into groups A-F. The cells in group A were not given any treatment; the cells in group B were incubated with 1 μmol/L α-melanocyte-stimulating hormone (α-MSH); the cells in groups C and D were treated with 1 μmol/L α-MSH, followed by the addition of kojic acid at concentrations of 50 and 100 μmol/L, respectively; the cells in groups E and F were treated with 1 μmol/L α-MSH, followed by the addition of compound 1-13 at concentrations of 50 and 100 μmol/L, respectively. Melanogenesis assay was used to measure the production of melanin by the cells in groups A-F. A total of 18 male C57BL/6J mice were divided into control group, model group, and treatment group, with 6 mice in each group. The mice in the model group and the treatment group were given intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while those in the control group were given intraperitoneal injection of an equal volume of normal saline; then the mice in the treatment group were given compound 1-13 by gavage, and those in the control group and the model group were given an equal volume of normal saline by gavage. The open field test was used to assess the motor function of mice in all three groups. Results The tyrosinase activity test showed that compound 1-13 could inhibit tyrosinase activity. MTT assay showed that different concentrations of compound 1-13 had no significant effect on the viability of B16F10 cells (P>0.05). Melanogenesis assay showed that compared with group B, groups C-F had a significant reduction in melanin production (F=328.70,q=16.42-47.47,P<0.01), and compared with group D, groups E and F had a significant reduction in melanin production (q=4.81,12.99,P<0.05). MTT assay showed that compared with group b, groups d-f had a significant increase in cell viability (F=138.50,q=4.21-21.33,P<0.05), and compared with group e, group h had a significant increase in cell viability (q=10.21,P<0.01). The open field test showed that compared with the model group, the treatment group had significant increases in the number of entries into the central zone, the distance traveled in the central zone, and the total distance traveled (F=15.47-19.62,q=6.07-7.56,P<0.01). Conclusion Compound 1-13 can suppress melanogenesis by inhibiting tyrosinase activity and alleviate PD-like injury.
Objective To investigate the clinical value of machine learning models based on radiomic features generated by habitat analysis of magnetic resonance imaging (MRI), including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), for the early diagnosis of prostate cancer. Methods MRI data of 111 patients with pathologically confirmed prostate lesions (82 cases of prostate cancer and 29 cases of benign prostate lesions) were retrospectively collected from two centers, namely the Shinan Campus and West Coast Campus of The Affiliated Hospital of Qingdao University, between January 2024 and August 2025. Habitat analysis was applied to extract radiomic features from the whole prostate gland region and suspected tumor regions on prostate MRI with two sequences (T2WI and DWI). The optimal number of clusters for habitat subregions was determined using the Calinski-Harabasz index. A three-step sequential method was adopted for radiomic feature selection. Based on the selected features, 11 machine learning models for early diagnosis of prostate cancer were constructed, with the optimal model selected via 5-fold cross-validation and grid search. The performance and clinical value of the model were evaluated using receiver operating cha-racteristic curves, calibration curves, and decision curve analysis. Results Habitat analysis demonstrated that MRI images of the whole prostate gland could be divided into 5 habitat subregions, while MRI images of suspected tumor regions were divided into 3 habitat subregions. A total of 38 core radiomic features of prostate cancer were finally selected through the three-step sequential method, based on which 11 diagnostic models for prostate cancer were established. Results of 5-fold cross-validation and grid search indicated that the optimal model was Light GBM constructed based on habitat features from regions of interest for the whole prostate gland on T2WI and DWI. Receiver operating characteristic curve showed that the model had good efficacy in diagnosing prostate cancer (AUC=0.942). Calibration curve and decision curve analysis indicated that the model had high accuracy and high clinical net benefit. Conclusion Whole-prostate habitat analysis combined with radiomic features from dual-sequence T2WI and DWI can more comprehensively capture the heterogeneous information of prostate cancer. The Light GBM model constructed accordingly can effectively improve the accuracy of early diagnosis of prostate cancer, providing a novel imaging solution for precise diagnosis and treatment of prostate cancer.
Glaucoma is the leading cause of irreversible blindness worldwide, with the core pathological features of progressive apoptosis of retinal ganglion cells (RGCs) and progressive damage to the optic nerve, and clinical interventions mainly aim to lower intraocular pressure, protect the optic nerve, and restore visual function. In recent years, cell-free exosome therapy derived from stem cells has emerged as a research hotspot in ophthalmic regenerative medicine due to its excellent biocompatibility, low immunogenicity, and strong ability to penetrate the blood-retinal barrier. Engineered exosomes can precisely target and act on diseased trabecular meshwork tissue through targeted modifications, effectively inhibit abnormal extracellular matrix deposition and the progression of fibrosis, reduce aqueous outflow resistance, and simultaneously exert a significant protective effect on RGCs, thereby providing new approaches for targeted therapy and neuroprotection in glaucoma. This article systematically reviews the fundamental mechanisms underlying exosome-based glaucoma treatment, the strategies for targeted modifications, the advances in preclinical research, and related challenges, in order to provide a reference for further in-depth research in this field.
Objective To investigate the clinical, genetic, and electrophysiological features of patients with familial cortical myoclonic tremor with epilepsy (FCMTE), and to improve the understanding of this disease. Methods A retrospective ana-lysis was performed for the clinical data of five probands with FCMTE who were treated in Qilu Hospital of Shandong University from January 2020 to December 2023, and pedigree investigations were conducted to analyze clinical symptoms and electrophysiological and genetic features. Results There were 28 patients (including the probands) in the five families, with an age of onset of 20-40 years. All pedigrees exhibited autosomal dominant inheritance spanning three or more consecutive generations. All patients had tremor and myoclonic seizures, and 22 patients had generalized tonic-clonic seizure (GTCS). Of all patients, 17 patients achieved seizure control after treatment with anti-seizure medications (ASMs), and their condition remained stable after follow-up for 1-5 years. Genetic testing revealed that three probands had an abnormal repeat expansion of the TTTCA/TTTTA pentanuc-leotide sequence in the SAMD12 gene; there were four probands with interictal epileptiform discharges on video-electroencephalography (VEEG) and one proband with giant somatosensory evoked potential (gSEP) and long-latency cortical reflex (C-reflex) on somatosensory evoked potential (SEP) testing. Conclusion FCMTE mainly manifests as adult-onset cortical myoclonic tremor and occasional GTCS, with the feature of autosomal dominant inheritance. Electrophysiological findings (interictal epileptiform discharges on VEEG, gSEP, and C-reflex on SEP) are crucial diagnostic indicators. The pedigrees in this study are mainly associated with repeat expansions in the SAMD12 gene, and long-read sequencing is recommended for detection. ASMs have a good clinical effect, and the disease often has slow progression.
Objective To investigate the influence of Epstein-Barr virus (EBV) on cholesterol metabolism pathways and ferroptosis-related pathways in Epstein-Barr virus-associated gastric cancer (EBVaGC) cells. Methods Transcriptomic sequencing and proteomic sequencing were performed for AGS and AGS-EBV cells, and differentially expressed genes and proteins were analyzed. Enrichment analyses and intersection analysis were used to evaluate the enrichment of differentially expressed genes and proteins in cholesterol metabolism pathways and ferroptosis-related pathways. Filipin Ⅲ staining was used to measure the level of cholesterol in AGS and AGS-EBV cells; RT-qPCR was used to measure the relative mRNA expression levels of 3-hydroxy-3-met-hylglutaryl-CoA synthase 1 (HMGCS1) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in AGS and AGS-EBV cells; Western blot was used to measure the protein expression levels of HMGCS1, HMGCR, and ferroptosis-related proteins in AGS and AGS-EBV cells. Results The results of transcriptomic sequencing and proteomic sequencing showed that compared with AGS cells, the differentially expressed molecules in AGS-EBV cells were highly enriched in the steroid biosynthesis pathway, and there were 44 differentially expressed ferroptosis-related genes and 24 differentially expressed ferroptosis-related proteins. Filipin Ⅲ staining showed that the level of cholesterol in AGS-EBV cells was significantly higher than that in AGS cells (t=15.16,P<0.05). The results of RT-qPCR showed that the relative mRNA expression level of HMGCS1 in AGS-EBV cells was significantly higher than that in AGS cells (t=3.66,P<0.05). Western blot showed that compared with AGS cells, AGS-EBV cells had significantly higher relative protein expression levels of HMGCS1, SOX2, FTH1, FTL, and GPX4 (t=3.26-7.28,P<0.05). Conclusion EBV infection can upregulate the expression of key enzymes in the cholesterol metabolism pathway in EBVaGC cells, while inhibiting ferroptosis in EBVaGC cells, and therefore, the cholesterol metabolism pathway and ferroptosis-related pathways are expected to become potential therapeutic targets for EBVaGC.
Objective To investigate the inhibitory effect of cadonilimab (anti-PD-1/CTLA-4) on hepatocellular carcinoma cells and its mechanism. Methods CCK-8 assay was used to assess the effect of different concentrations of cadonilimab (0, 0.3, 3, 30, 300, 3 000 nmol/L) on the viability of human hepatocellular carcinoma cell lines SMMC-7721 and HepG-2, and the concentration corresponding to the cell viability of approximately 70% was selected for subsequent experiments. SMMC-7721 cells were divided into groups A-D, and HepG-2 cells were divided into groups a-d. Groups A and a were control groups, groups B and b were cadonilimab treatment groups, groups C and c were PBMC treatment groups, and groups D and d were PBMC+cadonilimab treatment groups. Cell viability was measured for each group; wound healing assay was used to measure cell migration rate; Western Blot was used to measure the expression levels of the apoptosis-related proteins BCL2 and BAX; ELISA was used to measure the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) of each group of cells. Results CCK-8 assay showed that the viability of both SMMC-7721 and HepG-2 cells decreased with the increase in the concentration of cadonilimab (F=207.55,87.72,P<0.05), reaching approximately 70% at the concentration of 300 nmol/L, which was determined as the optimal concentration for subsequent experiments. There was a significant difference in cell viability between groups A-D and between groups a-d (F=117.63,113.81,P<0.05); group D had a significantly lower cell viability than group A, and group d had a signi-ficantly lower cell viability than group a (tDunnett=14.65,15.81,P<0.05). Wound healing assay showed that group D had a significant reduction in cell migration rate compared with group C, and group d also had a significant reduction compared with group c (t=21.45,59.61,P<0.05). Western Blot showed that compared with groups C and c, respectively, groups D and d had a significant increase in the relative protein expression level of BAX and a significant reduction in the relative protein expression level of BCL2 (t=4.15-60.88,P<0.05). ELISA showed that compared with groups C and c, respectively, groups D and d had significant increases in the secretion levels of IL-2 and IFN-γ (t=2.28-31.59,P<0.05). Conclusion Cadonilimab exhibits a significant antitumor activity against hepatocellular carcinoma cells and may kill hepatocellular carcinoma cells through immune activation.
Objective To investigate the value of coronary computed tomography angiography (CCTA) parameters in differentiating culprit plaques from non-culprit plaques in patients with acute coronary syndrome (ACS). Methods A retrospective analysis was performed for the clinical data of 350 patients with ACS who underwent percutaneous coronary intervention (PCI) at four medical centers from January 2017 to March 2024, including sex, age, medical history, and CCTA parameters of plaques. The patients were divided into a training set with 245 patients and a validation set with 105 patients at a ratio of 7∶3, and clinical data were compared between the two cohorts. Coronary plaques were divided into culprit plaque group and non-culprit plaque group, and CCTA parameters were compared between the two groups. The univariate and multivariate logistic regression analyses were used to identify the influencing factors for culprit plaques among CCTA parameters, and a diagnostic model for identifying culprit plaques in ACS was established based on these factors. The receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA) were used to assess the diagnostic efficiency, accuracy, and clinical practicability of this model. Results There were significant differences between the culprit plaques and the non-culprit plaques in the vessel involved, severity of coronary stenosis, plaque type, plaque position, total plaque volume, calcified plaque volume, lipid volume, fibrous vo-lume, fibrofatty volume, total plaque burden, lipid burden, fibrous burden, fibrofatty burden, positive remodeling, low-density plaque components, punctate calcification, and napkin ring sign (χ2=10.5-253.2,Z=10 923.5-97 879.5,P<0.05). The univariate logistic regression analysis showed that all CCTA parameters except plaque calcification burden were influencing factors for the formation of culprit plaques in ACS, and the multivariate logistic regression analysis showed that the vessel involved, the severity of coronary stenosis, plaque type, lipid volume of plaque, and punctate calcification of plaque were independent risk factors for culprit plaque. The model established for identifying ACS culprit plaques showed an area under the ROC curve of 0.878 in the training set and 0.855 in the validation set, suggesting that the model had good diagnostic performance. The calibration curve and DCA showed that the model had satisfactory calibration accuracy and good clinical applicability in both the training set and the validation set. Conclusion The model for identifying ACS culprit plaques based on multiple CCTA parameters has favorable discriminatory performance, high calibration accuracy, and good clinical applicability and can provide an important reference for the early diagnosis and treatment of ACS.
Objective To investigate the construction of a scoring model for preoperative differentiation between eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) subtypes among patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods A total of 180 patients with CRSwNP who were admitted to the Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University between January 2022 and December 2024 were enrolled. According to their subtypes, the patients were divided into an ECRSwNP group and an nECRSwNP group. General clinical characteristics, allergen sensitization status, hematological indices, and imaging parameters were collected and compared between the two groups. Indicators showing significant between-group differences were further subject to logistic regression analysis. A scoring model for differentiating CRSwNP subtypes was then established by assigning scores to these indicators according to their regression coefficients. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the clinical performance and accuracy of the model. Results Significant differences were observed between the two groups in atopic airway comorbidity, dust mite sensitization, shrimp/crab sensitization, ethmoid-dominant disease, history of sinus surgery, preoperative modified Lund-Kennedy endoscopic score, visual analogue scale (VAS) score for preoperative nasal symptoms, preoperative peripheral blood eosinophil count, eosinophil percentage, and systemic immune-inflammation index (χ2=8.151-28.982,Z=-5.854-2.011,t=-6.558,P<0.05). Logistic regression analysis showed that atopic airway comorbidity, dust mite sensitization, ethmoid-dominant disease, a preoperative modified Lund-Kennedy endoscopic score ≥10, a VAS score for preoperative nasal symptoms ≥6, and a preoperative peripheral blood eosinophil count ≥0.20×109/L were independent factors associated with the development of ECRSwNP subtype. A scoring model for differentiating CRSwNP subtypes was established by combining these indicators. ROC and calibration curve analyses showed that the model had good discriminative performance and accuracy (area under the curve=0.908). Conclusion Atopic airway comorbidity, dust mite sensitization, ethmoid-dominant disease, preoperative modified Lund-Kennedy endoscopic score, VAS score for preoperative nasal symptoms, and preoperative peripheral blood eosinophil count were closely associated with the ECRSwNP phenotype. The scoring model constructed based on these indicators showed good performance in differentiating CRSwNP subtypes.
Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD), which can occur at any stage of CKD, with an incidence rate of as high as 40%-80% in patients undergoing maintenance hemodialysis. Pharmacotherapies for SHPT in clinical practice mainly include phosphate binders, phosphate absorption inhibitors, vitamin D receptor agonists, and calcimimetics. In recent years, with the continuous clarification of the pathogenesis and drug targets of SHPT, several new therapeutic agents have emerged, such as tenapanor, colestilan, sustained-release calcitriol, and etelcalcetide. This article reviews the latest advances in pharmacotherapies for SHPT, so as to provide guidance for clinical treatment and new drug development for SHPT.
Peri-implantitis (PI) is a chronic inflammatory disease characterized primarily by inflammation of the surrounding mucosa and bone resorption around implants, and it is one of the most common complications of implant restoration. Current treatment regimens include non-surgical treatment (such as mechanical debridement, pharmacotherapy, laser therapy, and photodynamic therapy) and surgical treatment (including resective and regenerative surgery), but these methods cannot fully meet clinical needs. As a precise intervention strategy, targeted therapy can achieve precise blockade of pathological processes through specific identification and regulation of key molecular targets of the disease, with the advantages of high efficiency, low toxicity, and strong specificity. Although targeted therapy for PI is still in the stage of preclinical research, it has shown broad application prospects. Current studies mainly focus on cutting-edge fields such as gene polymorphisms, proteomics, and single-cell RNA sequencing. This article systematically reviews the potential molecular targets for PI-targeted therapy from the perspectives of functional genes and their associated protein products, microRNAs, long non-coding RNAs, and circular RNAs, in order to provide a reference for in-depth research and clinical translation in this field.
Objective To investigate the efficacy and safety of tirofiban in the treatment of acute progressive cerebral infarction (APCI). Methods A total of 88 patients with APCI were enrolled as subjects, and they were divided into treatment group and control group using a random number table, with 44 patients in each group. The patients in the control group received dual antiplatelet therapy (aspirin and clopidogrel) combined with conventional symptomatic treatment, and those in the treatment group received continuous intravenous infusion of tirofiban for 48 h, followed by dual antiplatelet therapy and conventional symptomatic treatment. The two groups were assessed in terms of National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) before treatment and on day 14 of treatment; the indicators of coagulation and platelets were measured and compared between the two groups, including platelet count (PLT), prothrombin time (PT), and platelet aggregation rate (PAgT) before treatment, at 48 hours of treatment, and on day 14 of treatment. Results Before treatment, there were no significant differences in NIHSS score and BI between the two groups (P>0.05), and on day 14 of treatment, both groups had a significant reduction in NIHSS score and a significant increase in BI (t=15.03-14.95,P<0.05); there were significant differences between the two groups in the changes in NIHSS score and BI after treatment (t=2.45, 2.68,P<0.05). Group, time, and group-time interaction had a significant impact on PAgT (Ftime=132.45,Fgroup=42.18,Finteraction=95.67,P<0.05), while they had no significant impact on PT and PLT (P>0.05). For the treatment group, PAgT level at 48 hours of treatment was significantly lower than that before treatment and on day 14 of treatment (P<0.05), and there was no significant difference between PAgT level on day 14 of treatment and that before treatment (P>0.05). Conclusion Tirofiban has good efficacy in the treatment of APCI and can effectively improve neurological deficits and enhance the activities of daily living, with a manageable safety profile.
Objective To investigate the clinical phenotype and genetic characteristics of a child with cardio-facio-cuta-neous syndrome (CFCS), and to evaluate the efficacy and safety of growth hormone therapy through a literature review. Methods Clinical data were collected from a child with CFCS and poor postnatal weight gain, and after confirmed diagnosis by whole-exome sequencing (WES), the patient was treated with long-acting recombinant human growth hormone (LA-rhGH) for one year. Growth parameters and safety indicators were closely monitored. A systematic literature review was performed for the reports of CFCS. Results A girl, aged 1 year and 4 months, presented with feeding difficulties and growth retardation after birth, with unsatisfactory improvement in growth after nutrition guidance and nutrient supplementation. The girl also had unusual facies, skin and hair abnormalities, and atrial septal defect. Genetic testing identified a de novo heterozygous missense mutation, c.1785T>G (p.F595L), in the BRAF gene, and thus the girl was diagnosed with CFCS. The girl received regular treatment with LA-rhGH at a dose of 0.2 mg/(kg·week) for one year. The annual height growth rate reached 12.5 cm/year; height Z-score was improved from -3.2 to -2.1, weight Z-score was improved from -2.8 to -1.9, and the serum level of insulin-like growth factor-1 (IGF-1) was increased from <15 μg/L before treatment to 96.8 μg/L. Follow-up during and after treatment showed that liver and kidney function parameters, blood glucose, thyroid function parameters, and tumor markers all remained within the normal range, and there were no other adverse effects. Conclusion For children with CFCS caused by a mutation in the BRAF gene, rhGH therapy can effectively promote the linear growth of body height and increase the serum level of IGF-1, with a favorable safety profile for short-term application. But long-term follow-up is needed to clarify its risk benefitratio.
Objective To investigate the effect and mechanism of aquaporin 5 (AQP5) on ferroptosis in lens epithelial cells (LECs). Methods Immortalized human LECs (SRA01/04 cells) were divided into empty lentiviral vector control group (group A), stable AQP5 knockdown group (group B), and stable AQP5 knockdown+mitochondria-targeted antioxidant treatment group (group C). Related kits were used to measure mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) fluorescence intensity; fluorescent probes were used to measure mitochondrial lipid peroxidation and the level of Fe2+; Western blot and immunofluorescence staining were used to measure the protein expression levels of Nrf2, SLC7A11, and GPX4. Results Compared with group A, group B had significant increases in the level of mtROS, the level of mitochondrial lipid peroxides, and the level of mitochondrial Fe2+ and significant reductions in MMP, the fluorescence intensity of mPTP and the relative protein expression levels of Nrf2, SLC7A11, and GPX4. Compared with group B, group C had significant reductions in the level of mtROS, the level of mitochondrial lipid peroxides, and the level of mitochondrial Fe2+ and significant increases in MMP, the fluorescence intensity of mPTP and the relative protein expression levels of Nrf2, SLC7A11, and GPX4 (F=5.66-46.17,q=2.88-9.32,P<0.05). Conclusion AQP5 deficiency can induce ferroptosis in LECs by inhibiting the Nrf2-SLC7A11-GPX4 axis. Maintaining or upregulating the expression level of AQP5 in LECs may become a potential strategy for the prevention of lens opacity and the treatment of cataract.
